In recent years, interest in the behaviour of free radicals in biological systems has increased. Radicals such as hydroxyl, peroxyl and superoxide radical anion have been implicated in a variety of cellular responses including aging, cancer, ischemic tissue injury and phagocytosis. Despite major efforts to study the role of free radicals in cell injury, identification of these reactive species remains a problem. The technique of spin trapping the free radicals has been used to address this difficulty. In this method, transient radicals are scavenged by appropriate nitrone or nitroso compounds to form persistent nitroxide adducts that can be identified spectroscopically. Currently used spin traps include 5,5-dimethylpyrroline-N-oxide (M.sub.2 PO,), 3,3,5,5-tetramethylpyrroline-N-oxide (M.sub.4 PO) and N-tert-butyl-.alpha.-phenylnitrone (PBN).
For example see J. Org. Chem. 1988 Vol. 53, 1566-1567 A. Dehnel et al and J. Med. Chem. 1988, Vol. 31, 428-432 G. M. Rosen et al. These references disclose the preparation and spin trapping properties of 3,3-dimethyl-5,5-disubstituted-4-carbethoxypyrroline N-oxide; 3,3,5,5-tetramethyl pyrroline N-oxide and 3,3-diethyl-5,5-dimethylpyrroline-N-oxide. These compounds are effective spin traps or scavengers for free radicals such as t-BuO*, *CH.sub.2 OH, *OH and Ph* with the half-lives of the adducts being several hours; however poor selectivity as well as poor solubility in water are evident.
It would be desirable to design other derivatives of pyrroline N-oxide having improved, additional and/or more selective spin trapping properties. We have prepared derivatives having other selected substituents in the 4-position, these substituents bestowing properties from among: extended adduct half life, enhanced selectivity toward specific free radicals, ability to bind to a wide variety of proteins, or other biological substrate and enhanced solubility in aqueous media.